Gastric cancer is the disease with the second cause of cancer death worldwide (Non-Patent Literature Document No. 1). In order to improve the prognosis of patients with gastric cancer and to ensure the quality of life (QOL) of the patients, the early detection of the gastric cancer is most important.
One of the reasons is because when the gastric neoplasia can be detected and treated at its early stage, it may be treated with a high degree of complete recovery.
As another reason, if the gastric cancer could be detected at a very early stage without its spreading to lymph nodes or other organs, a lesion may be resected by an endoscope while the gastric function is preserved. The endoscopic therapy for such an early gastric neoplasia may achieve a therapeutic outcome equivalent to the surgery, and patients may maintain the QOL at a level similar to that before the therapy.
Patients with early gastric cancer have usually no subjective symptoms of the neoplasia. Therefore, in order to make the early detection of the gastric cancer, a screening test by diagnostic imaging is generally recommended.
Among various diagnostic imaging methods, the gastroscopy (endoscopy in the stomach) is the most useful examination method for efficiently detecting early neoplasia because it allows a detection of subtle mucosal changes in color and surface pattern, which may be caused in the development of the early gastric neoplasia.
In addition, when a lesion can be detected by gastroscopy as being suspected as neoplasia, a specimen may be collected from the lesion by a biopsy using forceps through the endoscope, leading to a definitive histopathological diagnosis of the biopsy specimen.
From those advantages as described above, the gastroscopy is placed to be the most efficient examination for the early detection of gastric neoplasia.
In recent years, with the advancement of technology, a zoom endoscope that can magnify its optical observation up to eighty times was developed and applied in clinical practice.
The inventors have developed a technique to observe capillaries of the stomach by using the zoom endoscope (Non-Patent Literature Document No. 2) and detected a microvascular architecture that is characteristic of early gastric neoplasia (Non-Patent Literature Document No. 3). They have also applied these findings clinically to a screening examination for early gastric neoplasia and reported that these findings are useful for making an accurate diagnosis of the smaller and flat neoplasia (Non-Patent Literature Document No. 4). The present findings and the present zoom endoscopy technique are clinically applied not only in Japan but also widely around the world.
Furthermore, as a result of the observation by a zoom endoscope, the inventors have found that a lesion in the stomach may contain a white substance that does not transmit projected light into the epithelium of gastric epithelial neoplasia (adenoma or carcinoma) and that this white substance may disturb the observation of a subepithelial microvascular architecture that works as a marker of the diagnosis of the early gastric neoplasia. The nature, origin, and the like of this white substance was then unknown, therefore, the inventors named and reported the white substance as a white opaque substance (WOS) (Non-Patent Literature Document No. 5).
Recently, in addition to the zoom endoscope described above, an image-enhanced endoscopy such as a narrow-band imaging (NBI) has been developed. A combination of such an image-enhanced endoscopy technique with a zoom endoscope can allow a more clear observation of the structure of the epithelium, blood vessels and the like on the mucosal surface.
In the case when the endoscopic observation of the subepithelial microvessels was disturbed by the WOS in a lesion, an analysis of the morphological features of the WOS was carried out in combination of the NBI with a zoom endoscope (a NBI-combined magnifying endoscopy). As a result, it has been found that the WOS found in neoplastic lesions showed an irregular morphology, while that found in non-neoplastic lesions showed a regular morphology. Based on these findings, the present inventors have reported that the WOS could be a marker useful for the differential diagnosis between cancerous lesions and non-cancerous lesions (Non-Patent Literature Document Nos. 5 and 6).
Although the morphological features of the WOS became clear for making a histological diagnosis, the nature and origin of the WOS still remains unclear. In addition, a WOS can be recognized only in 50% of gastric epithelial neoplasia (adenoma or carcinoma). Therefore, it has been considered to be less feasible for clinical application of the WOS.